New WHI Analysis: Oral Contraceptives May Reduce CVD Risk

October 21, 2004

Andrew Bowser

Oct. 21, 2004 (Philadelphia) -- Women with a history of oral contraceptive use may be at decreased risk of adverse cardiovascular disease (CVD) outcomes, a recent analysis of data from the Women's Health Initiative (WHI) suggests.

The analysis, which included prospectively collected baseline data reported by more than 160,000 women, "suggests benefits of oral contraceptives in the prevention of [CVD] -- an important finding that contravenes previous studies on oral contraceptive use," said researcher Rahi Victory, MD, a fellow in the Division of Reproductive Endocrinology and Infertility at Wayne State University in Detroit, Michigan.

Previous studies have suggested an association between oral contraceptive use and increased risk of CVD, including stroke and myocardial infarction. However, according to Dr. Victory, those studies have been limited by small sample sizes, case-control methodologies, and limited control of associated risk factors, such as age, smoking, and weight.

Of the women in the WHI who reported taking oral contraceptives, approximately 15% also reported ever having CVD compared with 20% of women who did not report oral contraceptive use ( P < .001).

This difference translated into an 8% risk reduction in favor of oral contraceptive use (odds ratio [OR], 0.92; P < .001), according to Dr. Victory, who presented results here at the 60th annual meeting of the American Society for Reproductive Medicine.

Significant risk reductions were also seen for a variety of other self-reported cardiovascular outcomes, including hypercholesterolemia (OR, 0.89), myocardial infarction (OR, 0.90), peripheral vascular disease (OR, 0.88), and need for cardiac catheterization (OR, 0.92).

About one third of the 161,809 women analyzed reported oral contraceptive use. Women were between the ages of 50 to 79 years at enrollment.

Previous results reported from the randomized controlled trial portion of the WHI suggested considerable harm from hormone replacement therapy, including increased risk of adverse CVD outcomes such as coronary heart disease and stroke.

"The reason this is different from what was shown [previously] in the WHI is probably because those women went for a prolonged period of time without estrogen and then were re-exposed to estrogen," Dr. Victory told Medscape. "That's actually been shown in animal models to be detrimental.

"Here, what we are seeing is the effect of women who took oral contraceptives, so they were not going to be hypoestrogenic at any point," Dr. Victory continued. "They were going to be relatively well estrogenized for a prolonged period of time."

Longer use of oral contraceptives seemed to confer a greater benefit. For example, women reporting less than a year of oral contraceptive use were not at decreased risk of CVD (OR, 1.03; P = NS), whereas those who reported more than eight years of use were at considerably reduced risk (OR, 0.82; P < .001).

"With greater durations of use," Dr. Victory said, "you have progressive increases in risk reduction, all highly significant."

Dr. Victory told Medscape that molecular and animal data would support the hypothesis that oral contraceptives would protect against CVD risk.

At the molecular level, for example, it is likely that estrogen upregulates several different factors that contribute to good blood vessel integrity. Estrogen also reduces the amount of inflammatory mediators that contribute to atherosclerotic plaque formation, he explained.

Likewise, in hypoestrogenic or low-estrogen animal models, Dr. Victory said there is "good evidence" that "if you support them with estrogen throughout their lives into the postmenopausal [period], you do have a protective effect of estrogen."

Dr. Victory acknowledged the limitations of this retrospective analysis that depended on patient recall recorded in health questionnaires.

However, compared with other studies looking at oral contraceptive use and CVD risk, there are several strengths. Notably, the study population was large and well defined, data were available on multiple CVD end points, and investigators were able to control for a variety of potentially confounding risk factors such as smoking, diabetes, and use of hormone replacement therapy.

Michael Diamond, MD, director of the Division of Reproductive Endocrinology and Fertility at Wayne State University, said the results are "not definitive" but "provocative" and suggest a need for long-term, longitudinal studies focused on the effect of oral contraceptives on health outcomes.

"Right now, most branches of the [National Institutes of Health] have a time limit of five years [on longitudinal studies], so if you are talking about outcomes of 10, 20, or 30 years, that becomes very difficult in terms of how you are going to fund [a study] for those long periods of time," Dr. Diamond said in an interview with Medscape.

"It may be that there will be a need for new mechanisms of funding to allow those sorts of long-term studies to be conducted, not only for oral contraceptives, but all sorts of other issues as well, such as environmental exposure issues," Dr. Diamond said.

The analysis described by Dr. Victory was supported in part by a grant from the WHI.

ASRM 60th Annual Meeting: Abstract O-130. Presented Oct. 19, 2004.

Reviewed by Gary D. Vogin, MD

Andrew Bowser is a freelance writer for Medscape.

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